1. Field of the Invention
The present invention is related to a new microorganism Streptomyces exfoliatus YJ-118 and a method for producing pravastatin sodium represented in formula I by using this microorganism which shows a strong tolerance to ML-236B and a high hydroxylation activity of ML-236B to pravastatin. ##STR1##
2. Description of the Prior Art
An elevated plasma cholesterol level has long been recognized as a major risk factor for atherosclertic disease, and specifically for coronary heart disease. It was expected that plasma cholesterol could be reduced as a result of inhibition of cholesterol biosynthesis because more than 70% of the total input of body cholesterol is derived from de novo synthesis in humans. In 1975, ML-236B, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co A) reductase, a rate-limiting enzyme in the biosynthesis of cholesterol, was discovered in the culture broth of Penicillin citrium. After thorough screening of hundreds of microbial products as well as chemically or biologically modified derivatives of ML-236B, pravastatin sodium was chosen as a candidate for development, because of its stronger and more tissue-selective activity than the prototype compound.
Pravastatin has been produced by two-step fermentation: first, biosynthesis of ML-236B and second, bioconversion of this compound to pravastatin sodium. Lactone and carboxylate of ML-236B are represented in formula II-a and formula II-b, respectively. ##STR2##
wherein, R is H or Na.
It was reported that Streptomyces roseochromogenus NRRL-1233, Streptomyces roseochromogenus IFO-3363, Streptomyces roseochromogenus IFO-3411 (U.S. Pat. No. 4,346,227) and Streptomyces carbophilus SANK-62585 (Ferm BP-1145), Streptomyces halstedii IFO-3199 (JP No. Pyung 4-349034) transformed ML-236B to pravastatin. These bacteria, however, cannot tolerate a relatively high amount of ML-236B in the culture broth because of antibacterial activity of the substrate, and show low productivity of pravastatin.